Utility of measuring serum creatinine to detect renal compromise in ED patients receiving IV contrast-enhanced CT scan.

OBJECTIVE: The objectives of this study are to determine the efficacy of a roster of clinical factors in identifying risk for renal insufficiency in emergency department (ED) patients requiring intravenous contrast-enhanced CT scan (IVCE-CT) and to help mitigate potential for developing contrast-induced nephropathy (CIN). METHODS: A review was conducted of consecutive ED patients who received IVCE-CT during a 4-month period in our urban ED. The values of ED serum creatinine (SCr) performed were tabulated. The medical records of all patients with an elevated SCr (> 1.4 mg/dL) were reviewed to determine and correlate the presence of clinical risk factors for underlying renal insufficiency. RESULTS: During the 4-month study period, there were 2260 consecutive cases who received IVCE-CT; of these, 2250 (99.6%) had concomitant measurement of SCr. Elevated SCr occurred in 141 patients (6.2%); of these, 75 had a SCr > 2 mg/dL. In all, 139/141 (98.6%) with an elevated SCr had an underlying chronic or acute medical condition identified by medical record review which potentially compromised renal function, including chronic renal disease, diabetes mellitus, HIV infection, cancer, hypertension, congestive heart failure, sepsis/septic shock, chronic alcoholism, and sickle cell disease. Two patients with no identified risk factor each had (mildly) elevated SCr; both had a normal SCr measured post-CT scan. The total cost of performing serum basic metabolic panel to measure SCr in all patients during the 4-month study period was $94,500. CONCLUSIONS: Elevated SCr is rarely present in ED patients without recognized risk factors who receive IVCE-CT scan. The vast majority with underlying renal insufficiency are readily identified by a review of the patient's medical history and/or clinical findings. Routine SCr measurement on all ED patients regardless of risk stratification prior to IVCE imaging is neither time nor cost-effective.

An Ultraconserved Brain-Specific Enhancer Within ADGRL3 (LPHN3) Underpins Attention-Deficit/Hyperactivity Disorder Susceptibility.

BACKGROUND: Genetic factors predispose individuals to attention-deficit/hyperactivity disorder (ADHD). Previous studies have reported linkage and association to ADHD of gene variants within ADGRL3. In this study, we functionally analyzed noncoding variants in this gene as likely pathological contributors. METHODS: In silico, in vitro, and in vivo approaches were used to identify and characterize evolutionary conserved elements within the ADGRL3 linkage region (~207 Kb). Family-based genetic analyses of 838 individuals (372 affected and 466 unaffected patients) identified ADHD-associated single nucleotide polymorphisms harbored in some of these conserved elements. Luciferase assays and zebrafish green fluorescent protein transgenesis tested conserved elements for transcriptional enhancer activity. Electromobility shift assays were used to verify transcription factor-binding disruption by ADHD risk alleles. RESULTS: An ultraconserved element was discovered (evolutionary conserved region 47) that functions as a transcriptional enhancer. A three-variant ADHD risk haplotype in evolutionary conserved region 47, formed by rs17226398, rs56038622, and rs2271338, reduced enhancer activity by 40% in neuroblastoma and astrocytoma cells (pBonferroni < .0001). This enhancer also drove green fluorescent protein expression in the zebrafish brain in a tissue-specific manner, sharing aspects of endogenous ADGRL3 expression. The rs2271338 risk allele disrupts binding of YY1 transcription factor, an important factor in the development and function of the central nervous system. Expression quantitative trait loci analysis of postmortem human brain tissues revealed an association between rs2271338 and reduced ADGRL3 expression in the thalamus. CONCLUSIONS: These results uncover the first functional evidence of common noncoding variants with potential implications for the pathology of ADHD.